Imaging human intrasynaptic dopamine release by IV cocaine and amphetamine
- Johns Hopkins Medical Inst., Baltimore, MD (United States); and others
Intrasynaptic dopamine (DA) release was measured with C-11 Raclopride (RAC) PET in 15 human subjects with two psychostimulant drugs, IV cocaine or IV amphetamine (AMPH). Eleven cocaine users received IV saline then cocaine with high specific activity (SA) tracer RAC by IV bolus. To determine the optimal timing of drug administration, subjects received 48mg cocaine at 0 min.(1 subject), 4 min.(3 subjects) or 10 min.(7 subjects) post injection (mpi). One received 32mg at 4 and 16mg at 10 mpi. In a separate paradigm, the effect of AMPH not only on the binding of Hi SA but also on the receptor density (B{sub max}) using Hi SA and low SA was examined. Four normals received 2 pairs of Hi SA and Low SA RAC PET scans, each pair separated by 1 week to estimate 2 B{sub max}`s, one affected by AMPH. Before the 2nd pair, 0.3mg/kg IV AMPH was given in the times corresponding to the AMPH times for the 1s B{sub max} measurement. All were scanned on a GE 4096WB+PET with 50 frames over 90 min with radial arterial plasma sampling and HPLC metabolite correction. Neuropsychological-endocrine testing was done concurrently. All subjects had a marked psychophysiological response for cocaine or AMPH (less with Low SA RAC). However, evidence of substantial DA release was not consistent with IV cocaine nor correlated with any timing of cocaine vs. RAC, except for an overall trend for RAC reduction with cocaine. The % change in k{sub 3}/k{sub 4} by graphical analysis ranged from +10 to -21%, with similar changes by other methods of quantification, such as k{sub 3}/k{sub 4} constrained to cerebellar K{sub 1}/k{sub 2}, and simple tissue ratios comparisons. IV AMPH showed DA release (19% {plus_minus} 2 (SEM) decrease) in all Hi SA RAC (k{sub 3}/k{sub 4}) by graphical analysis. The calculation of B{sub max} in putamen using Scatchard analysis (baseline B{sub max}29{plus_minus}2) showed 12 to 28% decreases following AMPH.
- OSTI ID:
- 441578
- Report Number(s):
- CONF-950603-; ISSN 0161-5505; TRN: 96:002093-0002
- Journal Information:
- Journal of Nuclear Medicine, Vol. 36, Issue Suppl.5; Conference: 42. annual meeting of the Society of Nuclear Medicine, Minneapolis, MN (United States), 12-15 Jun 1995; Other Information: PBD: May 1995
- Country of Publication:
- United States
- Language:
- English
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